title: Regeneration of human dermis by a multi-headed peptide.
abstract: Skin aging is characterized by deterioration of the dermal collagen fiber network due to both decreased collagen expression and increased collagenolytic activity. We designed and evaluated in vitro and ex vivo the efficacy of a trifunctional peptide (TFP) to restore collagen and elastin fibers. TFP was constituted of an elastokine motif (VGVAPG)3, able to increase matrix constituent expression through the stimulation of the elastin-binding protein receptor, a GIL tripeptide occupying matrix metalloproteinase-1 subsites, and a RVRL linker domain acting as a competitive substrate for urokinase. The effects of TFP on type I, type III collagens, and elastin expression in dermal fibroblasts were determined by quantitative real-time reverse-transcriptase-PCR and western blotting. TFP's inhibitory capacity against MMP-1, plasmin, and urokinase was assessed using synthetic substrates, immunohistochemistry, and skin tissue sections as natural substrates. A skin explant model was used to recapitulate aging-induced dermal changes along culture extent. Collagen and elastin fiber structure was analyzed by two-photon fluorescence, second harmonic generation, and confocal microscopies. Compared with the different sections constituting the full peptide, we found that TFP activated the production of matrix constituents while inhibiting MMP-1 in vitro and ex vivo. It also induced a proper fiber network organization, reflecting the potency of TFP in skin remodeling and regeneration.
authors.affiliation: Regentis-International, University of Reims-Champagne Ardenne (URCA), Faculty of Medicine, SFR CAP Santé, Reims, France. Electronic address: joan.attia@regentis-international.com.
authors.forename: Joan
authors.initials: J
authors.lastname: Attia-Vigneau
authors.affiliation: Faculty of Medicine, Tissular and Cellular Imaging Center (URCA), Reims, France.
authors.forename: Christine
authors.initials: C
authors.lastname: Terryn
authors.affiliation: University of Reims-Champagne Ardenne (URCA)-FRE 3481 CNRS, MEdyc, SFR CAP Santé, Reims, France.
authors.forename: Sandrine
authors.initials: S
authors.lastname: Lorimier
authors.affiliation: Plastic Surgery Department, Courlancy Clinic, Reims, France.
authors.forename: Jerome
authors.initials: J
authors.lastname: Sandre
authors.affiliation: University of Reims-Champagne Ardenne (URCA)-FRE 3481 CNRS, MEdyc, SFR CAP Santé, Reims, France.
authors.forename: Frank
authors.initials: F
authors.lastname: Antonicelli
authors.affiliation: University of Reims-Champagne Ardenne (URCA)-FRE 3481 CNRS, MEdyc, SFR CAP Santé, Reims, France.
authors.forename: William
authors.initials: W
authors.lastname: Hornebeck
mesh_terms: D001706:Biopsy; D002478:Cells, Cultured; D003094:Collagen / Q000235:genetics / Q000378:metabolism; D020405:Dermis / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D015195:Drug Design; D004547:Elastic Tissue / Q000378:metabolism; D004549:Elastin / Q000235:genetics / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D020781:Matrix Metalloproteinase 1 / Q000235:genetics / Q000378:metabolism; D019278:Matrix Metalloproteinase 3 / Q000235:genetics / Q000378:metabolism; D010455:Peptides / Q000494:pharmacology*; D012038:Regeneration / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D015595:Skin Aging / Q000187:drug effects* / Q000235:genetics / Q000502:physiology
chemical_list: D010455:Peptides; D003094:Collagen; D004549:Elastin; C511768:MMP3 protein, human; D019278:Matrix Metalloproteinase 3; C522360:MMP1 protein, human; D020781:Matrix Metalloproteinase 1